A, B and H blood group antigens are found not only on red cells but also in body secretions. The FUT2 gene encodes a fucosyltransferase, and controls the secretor status and hence the expression of ABH antigens in secretions and endodermally derived tissues. The non-secretor status caused by null mutations in this gene is known to be associated with the susceptibility to many diseases. In the present study, the FUT2 gene was first amplified by polymerase chain reaction in 6 fragments covering all the putative coding sequence. The genetic heterogeneity of the FUT2 gene was then explored by a combination of single strand conformation polymorphism (SSCP) and heteroduplex analysis (HA) in a duplex format, and direct sequencing. The secretor phenotype was also determined by Lewis grouping and salivary testing. A total of 21 different single nucleotide polymorphisms (SNPs) were found in 79 Chinese and 20 Caucasian samples. Eight novel SNPs were identified in this study. Moreover, one novel in-frame 3-base insertion (V250-P25linsV) was also discovered. The FUT2 gene is highly polymorphic and its sequence variations have been found to be race specific. By comparing the frequencies and distribution of various sequence variations among different populations, close genetic relationship between Hong Kong Chinese and Mainland (in particular Guangzhou) Chinese was demonstrated. The secretor phenotype failed to reflect the underlying genotype in 3 samples. In particular, the 385A&gt;T mutation were found in both Le(a+b-) and Le(a+b+) individuals. Obviously, determination of secretor status by secretor phenotype alone is inaccurate. Thus, this demonstrated the importance of FUT2 genotyping. The 385A&gt;T mutation, which is not detected by conventional restriction digestion, is readily detected by heteroduplex analysis in the present study. This finding may allow the development of a simple screening protocol for the 385A&gt;T mutation in the future. Furthermore, during the course of multiplex SSCP and HA analysis, some slow-moving DNA bands, which stained black in silver staining, were discovered in all SSCP conditions used. They were absent when individual DNA fragment were analyzed by singleton SSCP analysis. It was hypothesized that they were duplexes formed from interaction of different amplicons and was given the name different-amplicon heteroduplex. It appeared that their existence might enhance the sensitivity of SSCP in identifying sequence variations.